The disclosure relates to methods of preparing (4bS,5aR)-12-cyclohexyl-N—(N,N-dimethylsulfamoyl)-3-methoxy-5a-((1R,5S)-3-methyl-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-4b,5,5a,6-tetrahydrobenzo[3,4]cyclopropa[5,6]azepino[1,2-a]indole-9-carboxamide (Compound I, formula I), its salts, and intermediates in the preparation of this compound. The compound has activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

Hepatitis C virus (HCV) is a major human pathogen, infecting an estimated 170 million persons worldwide. Hepatitis C virus (HCV) is the most common bloodborne infection in the USA and worldwide and is the leading cause of liver transplantation (Eric Chak et. al. Liver International 2011, 1090-1101). A substantial fraction of these HCV infected individuals develop serious progressive liver disease, including cirrhosis and hepatocellular carcinoma (Lauer, G. M.; Walker, B. D. N. Engl. J. Med. 2001, 345, 41-52).
A number of compounds which are inhibitors of HCV NS5B are in clinical development or have advanced to clinical studies and been discontinued for various reasons. More specific to this application, HCV NS5B inhibitors which bind to a site referred to in the art as Site 1, including Compound I, have been disclosed in U.S. Pat. No. 7,456,166 (issued Nov. 25, 2008; US patent publication 20070270405, published Nov. 22, 2007).
For purposes of large-scale production there is a need for a high-yielding synthesis of compound of formula I and related analogs that is both efficient and cost-effective.